Skin chemical carcinogenesis

Abstract

The purpose of this review is to update clinical dermatologists about current concepts of chemical carcinogenesis in skin. The incidence of skin cancer is increasing steadily and it has been estimated that of all new cancers diagnosed annually in the United States, almost one third originate in the skin. 1 Although solar radiation is the major cause of skin cancers, it is beyond doubt that chemicals also contribute substantially to the growing incidences of cutaneous neoplasms in humans. 2 The most common benign tumors induced by chemicals in experimental animals are papillomas and keratoacanthomas, whereas common malignancies are squamous cell carcinomas, basal cell carcinomas and melanomas. 3 Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and represent one of the few clearly defined classes of chemicals responsible for the development of skin cancers. 3 Humans are constantly exposed to PAHs through polluted air, cigarette smoke, automobile exhaust, and other air-borne pollutants. During the last four decades, it became clear that chemical carcinogenesis in murine skin, and possibly in human skin, is a stepwise process comprising at least three distinct stages: initiation, promotion, and malignant conversion. This is represented diagramatically in Figure 1-1. The initiation stage is essentially an irreversible step in which genetic changes occur possibly in gene(s) controlling differentiation. The promotion stage, on the other hand, leads to the formation of visible lesions through epigenetic mechanisms. This leads to the development of premalignant lesions (palillomas) which can then progress to malignant tumors (carcinomas). 3,4